Evaluation of potential multi-particulate drug delivery systems

Aruna Mummini Murty, University of Rhode Island


Multi-particulate tablets have the advantages of pellets and those of tablets. Formulation studies were performed on pellets using the granulation-extrusion-spheronization technique. The objective was to manufacture pellets of good quality with a high drug load and requisite dissolution rates. Inclusion of Ac-Di-Sol (cross linked sodium carboxymethylcellulose) increased the dissolution rate of drugs from clarithromycin and ciprofloxacin hydrochloride pellets. Surfactants such as cremophor (polyoxyl 35 castor oil) improved wetting of the drug and aided in the extrusion process. ^ A major problem in compaction of coated pellets is that the coating can rupture on compaction, this results in significant differences in dissolution profiles of coated pellets prior to and after compaction. A 28-4 fractional factorial design was used to evaluate the effect of selected factors on damage caused to coated pellets on compression. The factors evaluated were: drug (metronidazole, clarithromycin), pellet size (655μm, 925μm), polymer (Eudragit L30D-55 (polymethyl methacrylate), Aqoat ASLF (hydroxypropyl methylcellulose acetate succinate)), % polymer weight gain (25%, 55%), % of plasticizer (low, high), filler (Prosolv (silicified microcrystalline cellulose), lactose), % of coated pellets (30%, 60%) and compression force (15 kN, 30 kN). Statistical analysis was carried out on % leakage which is the difference in release of the drug from the coated pellets and their tablets in acidic dissolution medium at two hours. Pellet size was found to be the most significant factor (p = 0.003). The mean % leakage increased with pellet size in the tablet. However, when allowance was made for the difference between the pellet volumes of the large and small pellets, it was found that there was no evidence that the coating of the large pellets was more sensitive to compaction damage. Two-way interactions of pellet size with the type of drug (p = 0.047), the type of filler (p = 0.010) or compression force (p = 0.027) were also significant. ^ The results of this project indicate that it is possible to produce pellets, with a high drug loading, for which compression into tablets can be achieved with an acceptably low modification of dissolution profile. ^

Subject Area

Health Sciences, Pharmacy

Recommended Citation

Aruna Mummini Murty, "Evaluation of potential multi-particulate drug delivery systems" (2006). Dissertations and Master's Theses (Campus Access). Paper AAI3225324.